Background

About 50% of melanomas have an activating V600E BRAF mutation, which suggests that inhibition of the mutated BRAF kinase may be of clinical benefit. Previous phase I and II trials with vemurafenib have shown impressive response rates in V600E BRAF-mutated metastatic melanoma patients.1

Key findings

From January to December 2010, 675 patients were enrolled from 104 centres worldwide, and the cohorts were well-balanced.

Approximately two-thirds of patients in both arms had stage M1c disease, and 42% of patients had elevated LDH levels.

The data cut-off for this analysis was December 30, 2010.

At the pre-planned interim analysis (50% of deaths needed for final analysis), the hazard ratios (HR) for OS and PFS were 0.37 (95% CI 0.26–0.55; p <0.0001) and 0.26 (95% CI 0.20–0.33; p<0.0001), respectively, both in favour of vemurafenib. (Figures 1 and 2)

At six months, the estimated OS was 84% for vemurafenib, versus 64% for DTIC.

The median OS could not be analyzed at the time of this analysis.

Improvements in OS were seen for all sub-groups examined.

The median PFS was 5.3 months for vemurafenib, versus 1.6 months for DTIC, and was highly statistically significant in favour of vemurafenib.

All pre-specified subsets of patients showed clear benefits in PFS.

The ORR was 48.4% and 5.5% for vemurafenib and DTIC, respectively, among the 65% of patients evaluable for RR, to date.

As a result of the promising data, independent data monitoring committee (IDMC) recommended that the DTIC cohort has been allowed to cross over to vemurafenib.

At the time of analysis, 66% of vemurafenib patients and 25% of DTIC patients were still on treatment.